Several aging-related pathophysiological mechanisms have been described to contribute to the increased thrombotic risk in the elderly including oxidative stress, endothelial dysfunction, platelet and coagulation cascade activation. Antithrombotic treatment in the elderly should be individualized. Recent studies clarified some pathophysiological mechanisms of the enhanced oxidative stress and thrombotic alterations in older adults. In the last decade, randomized trials evaluated different antithrombotic strategies to reduce the risk of cardiovascular events in these patients. The proportion of elderly patients included in clinical trials is generally low, thus not reflecting the daily clinical practice. There is no consensus on the most appropriate antithrombotic treatment in elderly, also considering that bleeding risk management may be challenging in this high-risk subgroup of patients. Routine antiplatelet treatment is not a valid strategy for the primary prevention of cardiovascular events given the associated high risk of bleeding. In elderly patients with acute coronary syndrome, low-dose prasugrel or clopidogrel, shorter dual antiplatelet therapy and no pre-treatment before stent placement should be considered. Advanced age should not be the only reason for the underuse of oral anticoagulation in patients with atrial fibrillation, with direct oral anticoagulants to be preferred over warfarin for stroke prevention. Instead, a case-by-case clinical evaluation is warranted also based on patient's bleeding risk. There is a need for a structured tailored approach to manage thrombotic risk in elderly patients. The choice of the most appropriate antithrombotic treatment should balance efficacy and safety to reduce the risk of bleeding.